CN103396365A - Synthesis method of pyrazolone - Google Patents
Synthesis method of pyrazolone Download PDFInfo
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- CN103396365A CN103396365A CN2013103406489A CN201310340648A CN103396365A CN 103396365 A CN103396365 A CN 103396365A CN 2013103406489 A CN2013103406489 A CN 2013103406489A CN 201310340648 A CN201310340648 A CN 201310340648A CN 103396365 A CN103396365 A CN 103396365A
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Abstract
本发明涉及一种微波无溶剂快速合成3-甲基-1取代苯基-2-吡唑啉-5-酮的方法。在微波条件下，使用取代苯肼和乙酰乙酸乙酯快速合成，经乙酸乙酯重结晶得最后产物，具有不需溶剂、反应时间短、产率高等特点。The invention relates to a method for rapidly synthesizing 3-methyl-1 substituted phenyl-2-pyrazolin-5-one by microwave without solvent. Under microwave conditions, it is quickly synthesized by using substituted phenylhydrazine and ethyl acetoacetate, and the final product is obtained by recrystallization from ethyl acetate. It has the characteristics of no solvent, short reaction time and high yield.
Description
Technical field
The present invention relates to a kind of non-solvent microwave method of synthetic 3-methyl isophthalic acid-substituted-phenyl-2-pyrazolin-5-one fast.Under microwave condition, use substituted phenylhydrazines and methyl aceto acetate synthetic fast, obtain final product through re-crystallizing in ethyl acetate, having does not need that solvent, reaction times are short, the productive rate high.
Background technology
3-methyl isophthalic acid-substituted-phenyl-2-pyrazolin-5-one; it is a class cerebral protective agent (free-radical scavengers); mechanism research prompting; it can remove free radical; suppress lipid peroxidation; thereby suppress the oxidative damage of brain cell, vascular endothelial cell, neurocyte, particularly the 3-methyl-1-phenyl-2-pyrazolin-5-one effect is best.Therefore by clinical be used to improving the nervous symptoms that cerebral stroke at acute period occurs, action and the dysfunction of daily life.
In the technology of existing synthetic 3-methyl isophthalic acid-substituted-phenyl-2-pyrazolin-5-one, mostly by substituted phenylhydrazines and Butanonamide or methyl aceto acetate back flow reaction in ethanol or water, obtained.There is the problem in many synthesizing: as the raw material Butanonamide, be difficult to obtain; Make solvent with ethanol, increased cost on the one hand, the prior organic solvent of having introduced does not meet environment protection requirement; Substituted phenylhydrazines is added and is warmed up to 50 ℃ and adds methyl aceto acetate under uniform stirring again, and process is relatively numerous and diverse.Above-mentioned all factors cause being unfavorable for realizing scale operation, the popularization of 3-methyl isophthalic acid-substituted-phenyl-2-pyrazolin-5-one series products.
The present invention under microwave condition, uses substituted phenylhydrazines and methyl aceto acetate synthetic fast, through re-crystallizing in ethyl acetate, obtains 3-methyl isophthalic acid-substituted-phenyl-2-pyrazolin-5-one compounds, and having does not need that solvent, reaction times are short, the productive rate high.
Summary of the invention
The object of the present invention is to provide a kind of fast, 3-methyl isophthalic acid-substituted-phenyl that productive rate is high-2-pyrazolin-5-one preparation method.
Preparation method provided by the invention, under the microwave radiation condition, make substituted phenylhydrazines and methyl aceto acetate reaction, obtains 3-methyl isophthalic acid-substituted-phenyl-2-pyrazolin-5-one.
Reaction formula is as follows:
Wherein, R
1, R
2, R
3, R
4, R
5Can be respectively H, CH
3O or be no more than the alkyl of 3 carbon atoms.
In preparation method of the present invention, react under solvent-free condition.
The substituted phenylhydrazines of indication of the present invention refers to the compound as shown in the formula I:
Wherein, R
1, R
2, R
3, R
4, R
5Can be respectively H, CH
3O or be no more than the alkyl of 3 carbon atoms.
3-methyl isophthalic acid-the substituted-phenyl of indication of the present invention-2-pyrazolin-5-one refers to the compound as shown in the formula II:
Wherein, R
1, R
2, R
3, R
4, R
5Can be respectively H, CH
3O or be no more than the alkyl of 3 carbon atoms.
, through research of the present invention, in preparation method of the present invention, adopt the microwave of power 250 to 400W to carry out radiation.In preferred scheme, the microwave of employing 300 to 350W carries out radiation.In preferred scheme, adopt the microwave of 300W to carry out radiation.
In preparation method of the present invention, microwave irradiation time is controlled at 8 to 20 minutes.In preferred scheme, microwave irradiation time is controlled at 10 to 15 minutes.
In preparation method of the present invention, also comprise the re-crystallization step of using ethyl acetate under low temperature.
Embodiment
Embodiment 1
3-methyl isophthalic acid-p-methylphenyl-2-pyrazolin-5-one
get to procarbazine 12.2g (0.1mol), methyl aceto acetate 17.7ml (0.14mol), add in round-bottomed flask and shake, ultrasonic concussion 2min, connect reflux, put under normal pressure microwave reactor 300W microwave radiation the 10min that refluxes, obtain red thick liquid, add the dilution of 20ml methyl aceto acetate and 0.1g heating activated carbon backflow 5min, filtered while hot, be cooled to room temperature, 1/2 volume distillation washing 3 times, 1/2 volume saturated common salt washing 3 times, anhydrous magnesium sulfate drying, underpressure distillation, be dissolved in the 5ml ethyl acetate under 60 ℃ of gained white solids,-25 ℃ of lower crystallizations 10 hours, decompress filter, vacuum-drying obtained white solid 15.9g (0.0854mol) in 4 hours, productive rate 85.4%.mp134～125.5℃
Embodiment 2
3-methyl isophthalic acid-(2,3-3,5-dimethylphenyl)-2-pyrazolin-5-one
get 2, 3-dimethyl hydrazinobenzene 13.6g (0.1mol), methyl aceto acetate 17.7ml (0.14mol), add in round-bottomed flask and shake, ultrasonic concussion 2min, connect reflux, put under normal pressure microwave reactor 300W microwave radiation the 10min that refluxes, obtain the scarlet thick liquid, add the dilution of 20ml methyl aceto acetate and 0.1g heating activated carbon backflow 5min, filtered while hot, be cooled to room temperature, 1/2 volume distillation washing 3 times, 1/2 volume saturated common salt washing 3 times, anhydrous magnesium sulfate drying, underpressure distillation, be dissolved in the 5ml ethyl acetate under 60 ℃ of gained white solids,-25 ℃ of lower crystallizations 10 hours, decompress filter, vacuum-drying obtained white solid 16.2g (0.0807mol) in 4 hours, productive rate 80.7%.mp152～154.℃
Embodiment 3
3-methyl-1-phenyl-2-pyrazolin-5-one
get phenylhydrazine 10.8g (0.1mol), methyl aceto acetate 17.7ml (0.14mol), add in round-bottomed flask and shake, ultrasonic concussion 2min, connect reflux, put under normal pressure microwave reactor 300W microwave radiation the 10min that refluxes, obtain rose pink thick liquid, add the dilution of 20ml methyl aceto acetate and 0.1g heating activated carbon backflow 5min, filtered while hot, be cooled to room temperature, 1/2 volume distillation washing 3 times, 1/2 volume saturated common salt washing 3 times, anhydrous magnesium sulfate drying, underpressure distillation, be dissolved in the 5ml ethyl acetate under 60 ℃ of gained white solids,-25 ℃ of lower crystallizations 10 hours, decompress filter, vacuum-drying obtained white solid 14.3g (0.0821mol) in 4 hours, productive rate 82.1%.Mp126～128. ℃ (document: 127.5～128.5 ℃)
Embodiment 4
Take 3-methyl-1-phenyl-2-pyrazolin-5-one as example, investigated the impact on reaction yield of different microwave and reaction times, reaction process is with embodiment 1-3.
Claims (7)
Priority Applications (1)
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| CN2013103406489A CN103396365A (en) | 2013-08-06 | 2013-08-06 | Synthesis method of pyrazolone |
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| CN2013103406489A CN103396365A (en) | 2013-08-06 | 2013-08-06 | Synthesis method of pyrazolone |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107652237A (en) * | 2017-11-15 | 2018-02-02 | 天津瑞岭化工有限公司 | A kind of synthetic method of pyrazolone and its derivative |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101213189A (en) * | 2005-04-28 | 2008-07-02 | 拜耳医药保健股份公司 | 4-(pyridin-3-yl)-2-(pyridin-2-yl)-1,2-dihydro-3h-pyrazol-3-one derivatives as specific hif-prolyl-4-hydroxylase inhibitors for treating cardiovascular and haematological diseases |
| WO2010068717A2 (en) * | 2008-12-10 | 2010-06-17 | Auspex Pharmaceutical, Inc | Pyrazolinone scavengers of free radicals |
-
2013
- 2013-08-06 CN CN2013103406489A patent/CN103396365A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101213189A (en) * | 2005-04-28 | 2008-07-02 | 拜耳医药保健股份公司 | 4-(pyridin-3-yl)-2-(pyridin-2-yl)-1,2-dihydro-3h-pyrazol-3-one derivatives as specific hif-prolyl-4-hydroxylase inhibitors for treating cardiovascular and haematological diseases |
| WO2010068717A2 (en) * | 2008-12-10 | 2010-06-17 | Auspex Pharmaceutical, Inc | Pyrazolinone scavengers of free radicals |
Non-Patent Citations (1)
| Title |
|---|
| MOJTAHEDI, MOHAMMAD M.等: "Microwave-assisted synthesis of substituted pyrazolones under solvent-free conditions", 《HETEROCYCLIC COMMUNICATIONS》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107652237A (en) * | 2017-11-15 | 2018-02-02 | 天津瑞岭化工有限公司 | A kind of synthetic method of pyrazolone and its derivative |
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Application publication date: 20131120 |